On February 8, 2022 Hummingbird Bioscience, an innovative clinical-stage biotech company focused on developing precision therapies against hard-to-drug targets in cancer and autoimmune disease, reported the publication of preclinical data for HMBD-002, a novel anti-VISTA antibody therapeutic, in the Journal for ImmunoTherapy of Cancer, a peer-reviewed journal of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) (Press release, Hummingbird Bioscience, FEB 8, 2022, View Source [SID1234607937]).
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The publication highlights how HMBD-002, an IgG4 isotype anti-VISTA neutralizing antibody rationally developed with Hummingbird Bioscience’s Rational Antibody Discovery (RAD) platform, binds specifically and with high affinity to a binding site distinct from other published VISTA antibodies, and significantly inhibits tumor growth in syngeneic and humanized murine models of cancer. The data demonstrate that HMBD-002 inhibits VISTA binding to key partners, including VSIG3, to release suppression of T cell activity, and that HMBD-002 treatment results in remodeling of the tumor microenvironment in murine models towards an anti-tumor phenotype.
"We believe that VISTA has not been adequately drugged to date due to its complex biology that has complicated the discovery and testing of therapeutics that could achieve effective VISTA inhibition without causing unacceptable toxicity," said Dr. Jerome Boyd-Kirkup, Chief Scientific Officer, Hummingbird Bioscience. "Our preclinical data strongly supports that our differentiated anti-VISTA antibody HMBD-002, the development of which was uniquely enabled by our Rational Antibody Discovery platform, has potential as an important new therapy that may address VISTA-mediated immunosuppression across a broad range of tumors."
The publication, titled ‘Rationally targeted anti-VISTA antibody that blockades the C-C’ loop region can reverse VISTA immune suppression and remodel the immune microenvironment to potently inhibit tumor growth in an Fc independent manner’, can be accessed online.
HMBD-002 is currently being developed for patients with VISTA-expressing cancers, including triple-negative breast cancer and non-small cell lung cancer. The Phase 1 clinical trial NCT05082610 is open and enrolling.
About HMBD-002
HMBD-002 is an investigational IgG4 anti-VISTA antagonist antibody produced by our RAD platform to target the region where VISTA interacts with binding partners that have been shown to play an important role in modulating T cell activity, potentially unlocking the immune system to attack cancer cells. Due to complex biology, VISTA has not been adequately drugged to date. We believe HMBD-002 is the first Fc-independent anti-VISTA antibody designed to bind a computationally predicted functional epitope distinct from the epitopes of other known anti-VISTA antibodies in development. In the Company’s preclinical studies, HMBD-002 demonstrated potent anti-tumor activity both as monotherapy and in combination with pembrolizumab, in multiple syngeneic and humanized mouse models of cancers. HMBD-002 is being developed for various VISTA-expressing cancers, both as a monotherapy and in combination with pembrolizumab. The development of HMBD-002 is supported in part by a grant from the Cancer Prevention and Research Institute of Texas (CPRIT, DP190027).